Long Noncoding RNA Fos Downstream Transcript Is Developmentally Dispensable but Vital for Shaping the Poststroke Functional Outcome.
Background and Purpose: Stroke induces the expression of several long noncoding RNAs in the brain. However, their functional significance in poststroke outcome is poorly understood. We recently observed that a brain-specific long noncoding RNA called Fos downstream transcript (FosDT) is induced rapi...
| Publicado en: | Stroke (00392499) Vol. 52; no. 7; pp. 2381 - 2393 |
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| Autores principales: | , , , , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Lippincott Williams & Wilkins
Jul2021
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=151707160&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 151707160 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00392499 1FT jtl: Stroke (00392499) issn: 00392499 maglogo: N pubinfo: dt: Jul2021 vid: 52 iid: 7 pid: 433 pub: Lippincott Williams & Wilkins place: Baltimore, Maryland artinfo: ui: 151707160 151707160 NLM33940958 151707160 10.1161/STROKEAHA.120.033547 NLM33940958 151707160 ppf: 2381 ppct: 12 formats: tig: atl: Long Noncoding RNA Fos Downstream Transcript Is Developmentally Dispensable but Vital for Shaping the Poststroke Functional Outcome. aug: au: Mehta, Suresh L. Chokkalla, Anil K. TaeHee Kim Bathula, Saivenkateshkomal Chelluboina, Bharath Morris-Blanco, Kahlilia C. Holmes, Aleah Banerjee, Anik Chauhan, Anjali Juneyoung Lee Venna, Venugopal R. McCullough, Louise D. Vemuganti, Raghu Kim, TaeHee Lee, Juneyoung affil: Department of Neurological Surgery, University of Wisconsin-Madison. sug: subj: Stroke RNA Proteins Brain Recovery Physiology Rats Female Brain Metabolism Animal Studies Stroke Physiopathology Male Comparative Studies Multicenter Studies Evaluation Research Validation Studies Clinical Assessment Tools Funding Source Female Male ab: Background and Purpose: Stroke induces the expression of several long noncoding RNAs in the brain. However, their functional significance in poststroke outcome is poorly understood. We recently observed that a brain-specific long noncoding RNA called Fos downstream transcript (FosDT) is induced rapidly in the rodent brain following focal ischemia. Using FosDT knockout rats, we presently evaluated the role of FosDT in poststroke brain damage.Methods: FosDT knockout rats were generated using CRISPR-Cas9 genome editing on a Sprague-Dawley background. Male and female FosDT−/− and FosDT+/+ cohorts were subjected to transient middle cerebral artery occlusion. Postischemic sensorimotor deficits were evaluated between days 1 and 7 and lesion volume on day 7 of reperfusion. The developmental expression profile of FosDT was determined with real-time polymerase chain reaction and mechanistic implications of FosDT in the ischemic brain were conducted with RNA-sequencing analysis and immunostaining of pathological markers.Results: FosDT expression is developmentally regulated, with the adult cerebral cortex showing significantly higher FosDT expression than neonates. FosDT−/− rats did not show any anomalies in growth and development, fertility, brain cytoarchitecture, and cerebral vasculature. However, when subjected to transient focal ischemia, FosDT−/− rats of both sexes showed enhanced sensorimotor recovery and reduced brain damage. RNA-sequencing analysis showed that improved poststroke functional outcome in FosDT−/− rats is partially associated with curtailed induction of inflammatory genes, reduced apoptosis, mitochondrial dysfunction, and oxidative stress.Conclusions: Our study shows that FosDT is developmentally dispensable, mechanistically important, and a functionally promising target to reduce ischemic brain damage and facilitate neurological recovery. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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